Abstract:Xanthine oxidase（XOD）is used as a key enzyme in the metabolism of hypoxanthine and xanthine to produce uric acid in human body，but polyphenols can inhibit Xanthine Oxidase，thereby reducing uric acid synthesis and alleviating gout symptoms.To investigate the inhibition mechanism of polyphenols derived from natural products on XOD，the inhibition rate of XOD by several polyphenol monomers with good activity and inhibition kinetics of XOD were conducted，and the interaction between polyphenol monomers and XOD was simulated by fluorescence quenching experiment and molecular docking.Among the six polyphenol monomers，resveratrol，epigallocatechin gallate （EGCG）and hesperidin had better inhibitory effect on xanthine oxidase activity，and the IC50 of resveratrol，EGCG and hesperidin were 261.22，150.51，97.08 μmol/L，respectively，which were competitive inhibitors of XOD.Fluorescence quenching experiments showed that the binding of monomer to XOD caused the endogenous fluorescence of the enzyme to quench，and the quenching mechanism was static quenching.Molecular docking results showed that polyphenols could bind to amino acid residues of XOD and enter the molybdopterin （Mo-Pt）center or flavine-adenine dinucleotide （FAD）domain near the isoxazine ring to form a complex.Polyphenol monomers are effective competitive inhibitors，and can reduce uric acid levels by inhibiting the activity of XOD，which had a good prospect in the development of natural products and the application of functional food.